Human malaria is caused by species of parasitic organisms of the genus Plasmodium. It is transmitted by mosquitoes which ingest sexual forms of the parasite in blood meals. Sporozoite forms of the parasite develop in the mosquito and are transmitted to new host individuals bitten by the insect. The major human pathogen is Plasmodium falciparum.
Malaria is one of the most important health problems in underdeveloped, tropical countries. It is estimated that more than a billion people in the world inhabit areas in which malaria is transmitted. Although chloroquine has been used as an effective drug, this drug has some side effects, but more importantly, malarial parasites have acquired a resistance to chloroquine.
Thus, malaria has become an increasing problem in the tropical zones with the advent of chloroquine resistant strains of malaria parasites coupled with a decreased effectiveness of long acting insecticides such as DDT. The magnitude of the problem is reflected in the fact that malaria is the largest infectious disease in the world. Of the one billion people residing in malaria endemia areas, approximately 25 to 200 million people are diseased at any given time.
There are estimates of a million malaria deaths a year in Africa, chiefly among children under five. Even after surviving childhood infection, a large proportion of adults nonetheless remain susceptible to infection and show periodic parasitemia, even though their serum contains "protective" antiplasmodial antibodies. In hyperendemic areas of Africa, it is believed that nearly all residents harbor a continuous series of falciparum infections of low to moderate pathogenicity throughout their lives.
The problem of malarial infection has become even more serious as more strains of malaria have become resistant to the major anti-malaria drug chloroquine. More and more chloroquine resistant strains of Plasmodium falciparum have emerged in Central and South America, Africa, and Southeast Asia.
Researchers have synthesized chemical variants of chloroquine to combat new resistant malaria strains; however, these strains have already become resistant to the new drugs. Recently a new drug, mefloquine, was introduced, but already resistant strains have appeared. A totally new drug having chemical properties different from chloroquine is needed to stem the increasing epidemic of resistant malaria strains.
Pentamidine has been known for decades and was originally shown to be useful for the treatment of trypanosomiasis. Of more recent time, pentamidine has been found to be extremely useful in the treatment of pneumocystis carinii pneumonia, especially in immunocompromised patients suffering from the acquired immunodeficiency syndrome (AIDS). However, pentamidine has not heretofore been known to have utility in the treatment of malaria.
It goes without saying that in view of the magnitude of malaria infection throughout the world, and the lack of a satisfactory agent for the treatment thereof, an urgent need exists for a more-effective anti-Plasmodia agent having good therapeutic properties.